Each contractor will identify novel adjuvant candidates that can be used to augment the efficacy of human vaccines. Research performed under this award will contribute to the pipeline of new adjuvant leads that either: (a) exploit the natural capacity of the innate immune system to initiate and sustain effective T and B cell responses and to induce long term immune memory, or (b) act directly on cells of the adaptive immune system to enhance their response to pathogen-derived antigens. Studies include testing of adjuvant candidates with experimental or FDA approved preventative or therapeutic vaccines in relevant animal models to determine the potential efficacy of the vaccine against one or more pathogens relevant to human disease.